Formulating Opioids to Deter Abuse Remains a Challenge

BALTIMORE, Md.—Grinding, crushing, crisping, soaking, stirring. These are just some of the techniques drug abusers use to extract opioids from prescription medications. The question is, can opioids be formulated to deter abuse? That was the question addressed by a panel of presenters during the American Pain Society's 29th Annual Scientific Session here.

No one contests the negative public health effects of prescription opioid abuse, from initiation of drug use to medical emergencies, teenage suicide, crime, and death. However, not only do routes of administration vary by agent, the methods by which people abuse prescription opioids is not static, said Nathaniel Katz, MD, MS, of Tufts University School of Medicine and Analgesic Solutions, Natick, Mass., making it difficult to determine exactly how best to deter abuse.

A database that captured routes of administration (oral, snort, smoke, inject, other) of prescription opioids (hydrocodone, oxycodone, morphine, fentanyl, methadone, and hydromorphone) found that hydrocodone was mostly taken orally, while fentanyl was primarily smoked. Another study found that a subset of people who abuse opioids may begin taking a drug orally but then tamper with the agent so it can be snorted.

This creates a conundrum for pharmaceutical companies seeking to develop products intended to deter misuse and abuse. Recently, the U.S. Food and Drug Administration issued a memo cautioning “that language in a product's label for a claim of abuse resistance would require long-term epidemiological data from community-based observational studies that document changes in abuse and addiction and the consequences of those behaviors.” According to Edgar H. Adams, ScD, Covance, Conshohocken, Penn., who conducted an epidemiologic study of tramadol in the 1990s, a similar study today would cost approximately $10 million.

Another issue is that populations exposed to opioids are very broad; therefore, human abuse liability studies, which are required for all opioid agents, increasingly must serve as surrogates for “real world” behaviors, Lynn Webster, MD, of Lifetree Clinical Research & Pain Clinic in Salt Lake City, Utah, said.

The more difficult it is to extract an active ingredient from an opioid, the less likely people are to do so, noted Robert Bianchi, of the Prescription Drug Research Center, Fairfax, Va., who cited Web sites that help guide potential drug abusers, including details such as the pros and cons of smoking a specific extracted opioid. One unpublished study found 80% of subjects would spend a maximum of 3 to 10 minutes tampering with an agent with abuse as the goal.

A benefit of the majority of opioids having a claim of abuse resistance would be that patient care increases: physicians would be less wary of prescribing opioids, particularly in those at risk of abuse.

One hypothetical question remained unanswered: why are so many people abusing so many drugs?